We are using DOCK to screen compounds for activity against the known structure of HIV-1 reverse transcriptase. MidasPlus is an important tool to inspect the molecules and orientations chosen by DOCK. We survey about 500 molecules using MidasPlus and choose about 50 molecules. Our selection is based on the quality of each predicted binding mode as judged by our chemical intuition. We have been using the drug discovery program DOCK to look for inhibitors of HIV-1 reverse transcriptase (RT). This program screens a database of compounds for those which are complementary to the target structure, and therefore predicted to bind tightly. We started with a 2.8 A crystal structure of RT provided by Edward Arnold of Rutgers University. We used DOCK's program SPHGEN to identify structural pockets and then evaluated these pockets graphically using MidasPlus for their potential for inhibition. In addition to sites for competitive inhibition, we looked for sites which could interfere with domain motion and polymerization kinetics. Five pockets were chosen for DOCK runs. The docking studies are in progress. Currently, 50% of the compounds we tested show inhibition against RT at 10 micromolar concentration. Several are promising lead drug compounds. The CGL is useful for this work. Interactive graphics were heavily used in both the early stage of finding sites to target in RT and also in evaluating compounds selected by DOCK.